Project Summary The brain processes sensory information from the environment which, in turn, guides behavior. In olfaction, the decision to approach or avoid a stimulus is largely informed by correct assignment of an odor?s valence, or hedonic value. Furthermore, there are pronounced sex differences in odor valence that appear to be regulated by gonadal hormones, particularly estrogen. This has been well-characterized in studies involving ethologically relevant odors such as those that convey sociosexual information. However, there is also evidence that estrogen?s effects on olfaction are not limited to ethologically relevant odors and, in fact, generalize to odors that do not convey sociosexual information. It is unknown how the sexually differentiated brain represents odor valence and how estrogen impacts the formation of odor preferences. Odor valence processing occurs across olfactory structures. Among these, the olfactory tubercle (OT) stands out as being particularly important for direct control of odor-guided behavior due to its position within the ventral striatum, which receives modulatory dopaminergic input from the midbrain that informs decision-making. Work from our lab has demonstrated that the OT flexibly represents the associative valence of odors. Given the abundant expression of estrogen receptors in the ventral striatum, including the OT, and the pronounced responsivity of other ventral striatal structures to estrogen, this proposal seeks to identify the sex-dependent contributions of estrogen in the OT?s representation of odor valence, and in turn, its effects on odor preference. The proposed work will use behavior, in vivo electrophysiology, and region-specific pharmacology to test the hypothesis that estrogen enhances the representation of learned odor valence in the OT and contributes to learned odor preference. In Aim 1, I will demonstrate the sex-specific impact of local estrogen on the representation of odor valence in the OT. In Aim 2, I will determine the contribution of brain-derived estrogen to the expression of learned odor preferences. The findings from this work will ultimately reveal novel insights into the ways in which estrogen modulates olfaction and specifically, odor valence.